A crude mixture, called prostaglandin was reported by Goldblatt, Chem. Ind. London 52,1056 (1933); J. Physiol. London 84, 208 (1935) and von Euler, Arch. Exp. Path., Pharm. Abs. 175,78 (1934); 181 (1936); J. Physiol. 72,74 (1931); 81,102 (1934); 84,21 (1935); 88, 213 (1936); and Klin. Wschr. 14, 1182 (1935). Since then isolation, purification, preparation of derivatives and biological studies of the prostaglandins have continued. For example, microbiological conversions of unsaturated fatty acids with mammalian glandular tissue are described in U.S. Pat. Nos. 3,290,226 and 3,296,091. In U.S. Pat. No. 3,290,226 PGE compounds are described including PGE.sub.1, PGE.sub.2, and PGE.sub.3. The PGE series is characterized by the presence of the keto group at the 9-position in the cyclopentane ring. More recently, Ramwell et al, "Prostaglandins" in Progress in the Chemistry of Fats and Other Lipids, Vol. 9, edited by R. Holman, pp. 231-273, Pergamon Press, Oxford, 1968 refer to prostaglandin PGE.sub.1 as 11.alpha.,15(S)-dihydroxy-9-oxo-13-trans-prostenoic acid, PGE.sub.2 as 11.alpha.,15(S)-dihydroxy-9-oxo-5-cis,13-trans-prostadienoic acid and PGE.sub.3 as 11.alpha.,15(S)-dihydroxy-9-oxo-5-cis,13-trans, 17-cis-prostatrienoic acid. PGE.sub.1 is converted to dihydro-PHE.sub.1 by catalytic hydrogenation as described in Belgian Pat. No. 685,516. Following the prostanoic acid nomenclature, dihydro-PGE: is named as 11.alpha.,15(S)-dihydroxy-9-oxoprostanoic acid.
Pharmaceutically acceptable salts, for example, those of alkali metals and alkaline earth bases, such as the sodium, potassium, calcium and magnesium salts; those of ammonia or a basic amine such as mono-, di-, and triethyl amines, benzylamines, heterocyclic amines such as piperidine and morpholine, and amines containing water-solubilizing or hydrophilic groups such as triethanolamine, tris(hydroxymethyl)aminomethane, and phenylmonoethanolamine are described in U.S. Pat. No. 3,296,091. Carboxylate esters, wherein the esterfying radical has 1 to 8 carbon atoms inclusive, especially 1 to 4 carbon atoms, inclusive, illustratively the methyl, ethyl, butyl, cyclohexyl and octyl esters are formed by the usual methods, e.g., reaction with diazomethane or similar diazohydrocarbons as in U.S. Pat. No. 3,296,091. Acylates of lower alkanoic acids of 1 to 8 carbon atoms, inclusive, are prepared in the usual manner by reaction of the respective prostaglandin acids with the appropriate acid anhydride or acid halide, e.g., those of formic, acetic, propionic, butyric, isobutyric, valeric, caproic, caprylic and the like acids, as in Great Britain Pat. Spec. No. 1,040,544. Among these the acylates wherein the acyl radical has 2 to 4 carbon atoms are preferred, especially the acetate.
Biological studies of the prostaglandins, for example, actions on smooth muscle, reproductive system, nervous system, cardiovascular system, and relationship to lipid and carbohydrate metabolism, and miscellaneous effects are summarized by Bergstrom et al; "The Prostaglandins: A Family of Biologically Active Lipids," Pharmacological Reviews, Vol. 20, No. 1, p. 1 et sequitur, March, 1968, the Williams and Wilkins Company. Further biological studies include the effect of PGF.sub.2.sub..alpha. on isolated strips of human pregnant and non-pregnant myometrium in vitro. Bygdeman (1964) Acta. Physiol. Scand. 63, (suppl. 242), 1; Pickles and Hall (1963) J. Reprod. Fert. 6, 315 and Sandberg et al. (1965) Acta. Obstet, Gynec. Scand, 44, 585. Also Karim, S.M.M. (1966) J. Obstet, Gynaec. Brit. Cwlth. 73, 903 and Karim and Devlin (1967) ibid., 230 have shown that PGF.sub.2.sub..alpha. is present in human amniotic fluid obtained during labor. Further, Karim, British Med. J. 4, 618 (1968) has shown that PGF.sub.2.sub..alpha. appears in the maternal venous blood in variable amounts during labor.
It is against this background that the present invention has been conceived and embodied.